This is a 5-year study to evaluate the effect of a 10-week patient-partner telephone- based cognitive behavioral stress management (CBSM) intervention on chronic fatigue syndrome (CFS) symptoms in 150 patients diagnosed with CFS. Because many patients with CFS are unable to attend intervention sessions in clinical settings due to unpredictable periods of debilitating fatigue and limited mobility, we created a form of CBSM intervention that is delivered at the participant's home through a telecommunications system (i.e., Telephone-based CBSM, T-CBSM). A unique aspect of T-CBSM is that it uses the telephone to convene groups of individuals in their homes-thus it retains some of the supportive elements of a group-based intervention. We have observed that over a 5-month period this patient-focused T-CBSM intervention is associated with decreases in CDC-based CFS symptoms and decreases in the pro- inflammatory cytokines, interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) and increases in the anti-inflammatory cytokine, IL-13. Greater decreases in pro- inflammatory cytokines were associated with greater increases in the negative pitch of the AM-PM slope of salivary cortisol and greater decreases in CFS symptoms. This supported our neuroimmune model as an explanation for the effects of T-CBSM on CFS symptoms. We also conducted subgroup analyses comparing partnered and unpartnered CFS patients and found that the effects of the intervention were much larger in the partnered group. We have designed a study to follow up on these findings by testing a newly designed partner-patient dual focus videotelephone-delivered CBSM intervention (PP-T-CBSM) that allows the partner to learn stress management techniques with the patient in a group setting and to then practice together a set of stress management techniques such as relaxation and cognitive, behavioral and interpersonal skills training. We will compare changes in CFS symptoms, neuroimmune indicators, and psychosocial (patient and partner) functioning in participants assigned to PP-T-CBSM vs an attention time-matched telephone-based health information (T-HI) control condition in a 2 X 3 randomized experimental design with group (PP-T-CBSM, n=75 vs. T-HI, n=75) as the between-group factor, and time (Pre-intervention, 5- and 9- month follow-up) as the within-group factor.